【摘要】 目的:探讨重型弥漫性脑创伤后细胞外信号调节激酶1/2(ERK1/2)信号的改变及意义。方法:SD大鼠分为正常对照组、创伤组、ERK1/2抑制剂U0126高、低剂量组。Marmarou等法制作弥漫性脑创伤模型。伤后30min、1、6、24、48、72h光镜和电镜下观察伤后脑组织形态变化;Western blotting法检测海马区磷酸化ERK1/2和c-Fos蛋白表达;TUNEL法检测海马区凋亡细胞;伤后3-7d水迷宫法测试动物学习记忆功能。结果:伤后,创伤组脑组织损伤严重,神经细胞出现变性坏死和凋亡改变、神经轴索变性断裂;磷酸化ERK1/2蛋白表达在伤后30min明显增高,6h达高峰,高表达状态持续至伤后24h;c-Fos在伤后30min明显增高,6h达高峰,24h接近正常水平;神经细胞凋亡数目伤后6h明显增多,72h达高峰;大鼠搜索安全岛时间延长。U0126干预后,脑组织形态损伤程度、磷酸化ERK1/2和c-Fos表达、神经细胞凋亡数目回降;大鼠搜索安全岛时间缩短;上述变化在U0126高剂量组中更为显著。结论:ERK1/2信号途径参与大鼠重型弥漫性脑创伤病理损伤过程,并在伤后神经细胞凋亡进程中发挥关键作用。更多还原

【Abstract】 AIM:To investigate the effect of extracellular signal-regulated kinase 1/2 signaling pathway after severe diffuse brain injury (DBI) in rats,and to provide base for treatment. METHODS:Male Sprague-Dawley rats were randomly divided into four groups:control group,traumatic group,low dose of inhibitor U0126 treatment group and high dose of inhibitor U0126 treatment group. DBI rat model was established according to the description of Marmarou’s diffused brain injury. At 30 min and 1 h,6 h,24 h,48 h and 72 h after injury,morphological changes were observed under light and electronic microscopes. The ERK1/2 phosphorylation and c-Fos were measured by Western blotting. Apoptosis was measured with TUNEL method. Learning and memory function were performed with Morris water maze from 3 days to 7 days after injury. RESULTS:After trauma,some neurons displayed histopathologic changes of necrosis and apoptosis,axon myelin sheath internalization and disconnection. ERK1/2 phosphorylation protein was apparently increased at 30 min after injury,approached peak at 6 h and continued to 24 h. c-fos protein was markedly increased at 30 min after injury,approached peak at 6 h and returned to bottom at 24 h. The number of apoptotic nerve cells increased at 6 h after and approached peak at 72 h. Latencies of searching safety island prolonged. Rats treated with U0126 had reduction in ERK1/2 activity,c-Fos protein,neuronal apoptosis and searching safety island latencies. CONCLUSION:The activated ERK1/2 signaling pathway plays an important role in processing of nerve cell apoptosis after severe DBI.更多还原